This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. A. Specific Aims The goal of this proposal is to determine the functional significance of prohibitins during 3T3-L1 adipocyte differentiation. Our preliminary data showed that both of these prohibitins (PHBs), including PHB1 and PHB2 (repressor of estrogen receptor activity, REA), were significantly increased during the adipocyte differentiation of 3T3-L1 preadipocytes. Moreover, 3T3-L1 adipocyte differentiation was impaired after the simultaneous knockdown of either PHBs protein by siRNA-PHB1 or siRNA-REA. So, our first aim is to determine whether PHB1 and PHB2 are critical factors in promoting mouse 3T3-L1 adipocyte differentiation. Our second aim is to investigate the signaling pathway of PHB1 and PHB2 during 3T3-L1 cell adipogenesis.